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<p>The induction of cuproptosis, a recently identified form of copper-dependent non-apoptotic cell death, offers a promising strategy to enhance the efficacy of chemotherapeutic antitumor treatments. However, efficiently delivering copper ions into tumor mitochondria to robustly trigger cuproptosis while simultaneously potentiating chemotherapy remains a major challenge. Herein, we develop a cuproptosis-inducing nanodrug constructed via amino acid-assisted cooperative coordination self-assembly of copper ion, the copper ionophore elesclomol (ES), and the linical chemotherapeutic agent docetaxel (DTX) to augment chemo-immunotherapy of prostate cancer. Once internalized by tumor cells, the obtained nanodrugs gradually degrade to release copper ions and ES, which together promote the aggregation of lipoylated proteins and the depletion of Fe-S cluster proteins, thereby activating cuproptosis and amplifying DTX-mediated chemotherapy. Moreover, the nanodrugs elicit robust immunogenic cell death through the combined actions of cuproptosis and DTX-induced apoptosis, further boosting antitumor immune responses. Overall, the multicomponent co-assembled nanodrugs demonstrate excellent antitumor activity both in vitro and in vivo by integrating cuproptosis induction, chemotherapy enhancement, and immune activation, highlighting their strong potential for clinical translation in prostate cancer therapy.</p>

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Clinical chemotherapeutic agent coordinated copper-elesclomol nanomedicine potentiates cuproptosis for high-efficiency chemo-immunotherapy of prostate cancer

  • 期刊论文

  • 发表日期：

    2026年1月16日

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  • Ming Liu,
  • Xianzhou Jiang,
  • Bing Zhang,
  • Zehua Wang,
  • Yanhui Zhang

摘要

The induction of cuproptosis, a recently identified form of copper-dependent non-apoptotic cell death, offers a promising strategy to enhance the efficacy of chemotherapeutic antitumor treatments. However, efficiently delivering copper ions into tumor mitochondria to robustly trigger cuproptosis while simultaneously potentiating chemotherapy remains a major challenge. Herein, we develop a cuproptosis-inducing nanodrug constructed via amino acid-assisted cooperative coordination self-assembly of copper ion, the copper ionophore elesclomol (ES), and the linical chemotherapeutic agent docetaxel (DTX) to augment chemo-immunotherapy of prostate cancer. Once internalized by tumor cells, the obtained nanodrugs gradually degrade to release copper ions and ES, which together promote the aggregation of lipoylated proteins and the depletion of Fe-S cluster proteins, thereby activating cuproptosis and amplifying DTX-mediated chemotherapy. Moreover, the nanodrugs elicit robust immunogenic cell death through the combined actions of cuproptosis and DTX-induced apoptosis, further boosting antitumor immune responses. Overall, the multicomponent co-assembled nanodrugs demonstrate excellent antitumor activity both in vitro and in vivo by integrating cuproptosis induction, chemotherapy enhancement, and immune activation, highlighting their strong potential for clinical translation in prostate cancer therapy.